Servicio de Neumología, Hospital San Pedro de Alcántara, Cáceres, España.
Arch Bronconeumol. 2017 Dec;53(12):682-687. doi: 10.1016/j.arbres.2017.06.016. Epub 2017 Aug 18.
Recent research on the relationship between the immune system and cancer has revealed the molecular mechanisms by which cancer cells co-opt certain T cell receptors which block the cytotoxic response to defend themselves from the antitumor immune attack. These findings have helped identify specific targets (T cell receptors or their corresponding ligands) for the design of monoclonal antibodies that can unlock the immune response. These drugs, known as immune checkpoint inhibitors, have shown efficacy in metastatic melanoma and kidney cancer, and have been successfully tested in non-small cell lung cancer in recent trials. Immune checkpoint inhibitors were included in clinical practice as a second-line option after an initial chemotherapy (CT) regimen, and in the last year positive results have been reported from randomized trials in which they were compared in first line with standard CT. Responses have been surprising and durable, but less than 20%-25% in unselected patients, so it is essential that factors predicting efficacy be identified. One such biomarker is PD-L1, but the different methods used to detect it have produced mixed results. This non-systematic review discusses the results of the latest trials, the possibilities of incorporating these drugs in first-line regimens, the criteria for patient selection, adverse effects, and the prospects of combinations with conventional treatment modalities, such as CT, radiation therapy, and antiangiogenic agents.
最近关于免疫系统和癌症之间关系的研究揭示了癌细胞利用某些 T 细胞受体的分子机制,这些受体阻止细胞毒性反应,从而保护自己免受抗肿瘤免疫攻击。这些发现有助于确定特定的靶点(T 细胞受体或其相应的配体),用于设计能够解锁免疫反应的单克隆抗体。这些药物被称为免疫检查点抑制剂,已在转移性黑色素瘤和肾癌中显示出疗效,并在最近的试验中在非小细胞肺癌中成功进行了测试。免疫检查点抑制剂被纳入临床实践,作为初始化疗(CT)方案后的二线选择,在去年的随机试验中报告了阳性结果,其中它们与标准 CT 进行了一线比较。反应令人惊讶且持久,但在未经选择的患者中不到 20%-25%,因此确定预测疗效的因素至关重要。一种这样的生物标志物是 PD-L1,但用于检测它的不同方法产生了混合结果。本非系统性综述讨论了最新试验的结果,将这些药物纳入一线方案的可能性,患者选择标准,不良反应以及与常规治疗方式(如 CT、放射治疗和抗血管生成剂)联合的前景。